Synthesis of Isoquinolines via the [4+2] Cycloaddition Reaction of Oxazoles and Arynes

Herein, we report our investigations on the reaction of a variety of substituted oxazoles with o-(trimethylsilyl)aryl triflates promoted by potassium fluoride and 18-crown-6-ether. Several functionalized isoquinoline compounds were obtained in moderate to good yields when the transformation was carried out at room temperature, followed by acidic workup, presumably via a [4+2] cycloaddition-ring-opening reaction pathway. Alternatively, bicyclic ethers were produced in reasonable yields when performing the transformation at 60 degrees C via a sequence of [4+2] cycloaddition, retro-Diels-Alder, and [4+2] cycloaddition reactions.

Automated summary

In this study, we investigated the reaction of several substituted oxazoles with o-(trimethylsilyl)aryl triflates promoted by potassium fluoride and 18-crown-6-ether. We obtained functionalized isoquinoline compounds in moderate to good yields at room temperature through a [4+2] cycloaddition-ring-opening reaction pathway, followed by acidic workup. Alternatively, bicyclic ethers were produced in reasonable yields at 60 degrees C through a sequence of [4+2] cycloaddition, retro-Diels-Alder, and [4+2] cycloaddition reactions.